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PEG-liposomal oxaliplatin induces apoptosis in hunman colorectal cancer cells via Fas/FasL and caspase-8.
MedLine Citation:
PMID:  21888623     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Abstract Cellualr uptake of PEG-liposomal oxaliplatin induces bioactive changes in colorectal cancer, thus we investigated the apoptotic effect and anticancer mechanism of PEG-liposomal oxaliplatin. We treated the human colorectal cancer SW480 cell line with PEG-liposomal oxaliplatin and Caspase-8 inhibitor (Z-IETD-FMK). We evaluated apoptosis using flow cytometry (FCM) and Terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick end labelling (TUNEL) assay. Expression of Fas/FasL and Cytochrome C was detected using FCM and Immunofluorescence assay. Expression of Caspase-8, Bid, Caspase-9, Caspase-7, and activated Caspase-3 (P17) was observed in the Western blot analyses. Our results indicated that PEG-liposomal oxaliplatin (containing 28 μg/ml oxaliplatin) markedly induced apoptosis in SW480 cells compared with 28 μg/ml free oxaliplatin. The expression levels of Fas, FasL, Cytochrome C, Caspase-9, Caspase-7, and activated Caspase-3 proteins were up-regulated with a corresponding increase in apoptosis, however, the expression levels of Caspase-8 and Bid were down-regulated as apoptosis increased. When cells were treated with Z-IETD-FMK, apoptosis was inhibited but there was little impact on the expression of Fas, FasL, Cytochrome C, Bid, Caspase-9, Caspase-7, and activated Caspase-3. These findings indicate that PEG-liposomal oxaliplatin enhanced the anticancer potency of the chemotherapeutic agent; moreover, Fas/FasL and Caspase-8 signaling pathways play a key role in mediating PEG-liposomal oxaliplatin-induced apoptosis.
Authors:
Chuang Yang; Hai-Zhong Liu; Zhong-Xue Fu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-2
Journal Detail:
Title:  Cell biology international     Volume:  -     ISSN:  1095-8355     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9307129     Medline TA:  Cell Biol Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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